Universität zu Köln

M. Leite, Diana, Seifi, Mohsen ORCID: 0000-0002-5795-4409, Ruiz-Perez, Lorena, Nguemo, Filomain, Plomann, Markus, Swinny, Jerome D. and Battaglia, Giuseppe (2022). Syndapin-2 mediated transcytosis of amyloid-beta across the blood brain barrier. Brain Commun., 4 (1). OXFORD: OXFORD UNIV PRESS. ISSN 2632-1297

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Abstract

A deficient transport of amyloid-beta across the blood-brain barrier, and its diminished clearance from the brain, contribute to neurodegenerative and vascular pathologies, such as Alzheimer's disease and cerebral amyloid angiopathy, respectively. At the blood-brain barrier, amyloid-beta efflux transport is associated with the low-density lipoprotein receptor-related protein 1. However, the precise mechanisms governing amyloid-beta transport across the blood-brain barrier, in health and disease, remain to be fully understood. Recent evidence indicates that the low-density lipoprotein receptor-related protein 1 transcytosis occurs through a tuhulation-mediated mechanism stabilized by syndapin-2. Here, we show that syndapin-2 is associated with amyloid-beta clearance via low-density lipoprotein receptor-related protein 1 across the blood-brain barrier. We further demonstrate that risk factors for Alzheimer's disease, amyloid-beta expression and ageing, are associated with a decline in the native expression of syndapin-2 within the brain endothelium. Our data reveals that syndapin-2-mediated pathway, and its balance with the endosomal sorting, are important for amyloid-beta clearance proposing a measure to evaluate Alzheimer's disease and ageing, as well as a target for counteracting amyloid-beta build-up. Moreover, we provide evidence for the impact of the avidity of amyloid-beta assemblies in their trafficking across the brain endothelium and in low-density lipoprotein receptor-related protein 1 expression levels, which may affect the overall clearance of amyloid-beta across the blood-brain barrier.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code M. Leite, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Seifi, Mohsen UNSPECIFIED orcid.org/0000-0002-5795-4409 UNSPECIFIED Ruiz-Perez, Lorena UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED Plomann, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Swinny, Jerome D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Battaglia, Giuseppe UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-688533
DOI:	10.1093/braincomms/fcac039
Journal or Publication Title:	Brain Commun.
Volume:	4
Number:	1
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	2632-1297
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALZHEIMERS-DISEASE; MEMBRANE INVAGINATION; APOLIPOPROTEIN-J; RAB GTPASES; RECEPTOR; PEPTIDE; CLEARANCE; EXPRESSION; TRANSPORT; PROTEIN Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68853